Question

Discuss the female reproductive cycle. Detail the timeline and hormones that drive the process and what happens during the cycle from start to finish.

Answer 1

The female reproductive cycle is primarily composed of the ovarian cycle occurring in ovaries and the menstrual cycle occurring in the uterine endometrium. Endometrium is the innermost lining of the uterus that is composed of endometrial glandular epithelium, luminal epithelium and stroma. The embryo is known to attach to the luminal epithelium which is derived from glandular epithelium. The menstrual cycle is responsive to the hormones that are secreted by ovarian cycle. Hence, events in the ovarian cycle are indicated in menstrual cycle events.

The human menstrual cycle is typically around 28 ± 2 days. Consider the average menstrual cycle to be around 28 days. Based on a 28 day menstrual cycle, timelines have been indicated. The menstrual cycle is divided into three phases- menstruation, follicular and luteal phase.

Menstruation: Menstruation or Menses occurs between day 1-5 in the menstrual phase. It is characterized by visible bleeding caused by loss of endometrial tissue. Menstruation sets in due to decrease in estrogen and progesterone hormone production by the ovary. Estrogen is produced by the granulosa cells while progesterone is produced by corpus luteum. As there was no embryo implantation occurring in previous cycle, the corpus luteum will regress and stop production of progesterone. The estrogen production by ovarian granulosa cells in also low. Hence, endometrial cells will undergo apoptosis and will be lost. Loss of endometrium will expose the blood vessels, causing blood loss during menses. During menstruation, a dominant follicle is selected from all the growing follicles in the ovaries.

The dominant ovarian follicle will grow and its granulosa cells will start producing estrogen in response to follicle stimulating hormone or FSH production by pituitary (via GnRH in hypothalamus). Estrogen is mitogenic and causes proliferation of endometrial glands and stroma. Increased estrogen production will cause increase in endometrial thickens and bleeding will stop.

Follicular or Proliferative Phase: Day 6-13 is the follicular or proliferative phase, where FSH released by the anterior pituitary in response to GnRH will stimulate proliferation of granulosa cells. Granulosa cells will secrete estrogen in response to FSH. FSH actions will cause growth of mature dominant antral follicle. Estrogen will cause endometrium to thicken and grow. Both glandular epithelium and stromal cells divide in response to estrogen.

Ovulation: Day 14 is the ovulation day. Hypothalamus GnRH will stimulate Luteinizing (LH) hormone when estrogen levels are peaked in circulation. LH stimulates ovulation by inducing production of intra-follicular proteolytic enzymes within 12hr of its secretion. These enzymes break the follicle releasing the ova, causing ovulation. During ovulation, the ova along with attached granulosa cells are released. However, theca cells of dominant follicle will remain behind to form corpus luteum. Fertilization can occur if there is sperm present, leading to zygote formation. Zygote can divide to 2 celled. 4 celled, 8 celled embryo and so on.

Luteal or Secretory phase: This phase is between days 15-28 of menstrual cycle. Upon ovulation, theca cells will form corpus luteum. They start secreting progesterone hormone; Progesterone reaches the endometrium via uterine arteries and will induce differentiation of endometrial glandular epithelium and stroma. Stroma changes to decidual cells, which are large cells with foamy cytoplasm. These cells will grow and start synthesizing and storing protein and nutrients that may be required by embryo for growth. If embryo is present, it enters the endometrial lumen in blastocyst stage between days 19-24 (implantation window). Implantation can occur followed by invasion into the endometrium. If there is no embryo, then corpus luteum will regress and the progesterone levels decline. There is minimal estrogen production in secretory phase. Due to low progesterone and estrogen levels, menstruation will set in, ending the luteal phase.